: The Chicken or the Egg Hypothesis of PNH and Hypoplastic MDS: They may be either

PNH clones may be pre-existing

MDS clones may also be pre-existing

Not all normal karyotypes are normal:

Evidence the detection of pre-existing MDS clones by more sensitive SNP-array karyotyping

WE THEORIZE that there may be significant pre-existing PNH and MDS clones that trigger the initial immune response resulting in autoimmunity to hematopoietic stem cells in some patients

WE HYPOTHESIZE that the late emergence of PNH/MDS results from an immune response to either an abnormal clone or normal stem cells - destroying stem cells while somehow favoring the emergence of that pre-existing clone or a new clone (MDS or PNH) having a selective advantage. Selection of a 6p-clone removing the target of immune destruction (Betensky, ASPHO 2015)